The influence of muramyl dipeptide (N-acetylmuramyl-L-alanyl-D-isoglutamine) on the rejection of mouse skin allografts was investigated. While the 0.1-mg dose administered on days 7, 6, 5 prior to transplantation caused significant prolongation of the graft survival, the 0.5-mg dose administered on days 3, 2, 1 prior to transplantation resulted in remarkable augmentation of the graft rejection. The present results support the view that muramyl dipeptide can induce both stimulatory and suppressive immune mechanisms, depending on the treatment regimen.